One-third of neonates weighing less than 2500 grams are not premature but term infants whose growth has been retarded in utero. These infants have an increased incidence of perinatal problems, decreased stature and long-term neurologic sequelae. Growth retardation appears to be caused by an inadequate flow of nutrients and oxygen across the placenta into the fetus. We have been investigating whether intrauterine, nutritional supplements can be used to treat growth retardation and have found that fetal, intragastric supplementation will prevent the development of growth retardation in fetuses of malnourished mothers. Our aims now are to determine: 1) if supplementation will increase growth in normal fetuses and fetuses growth retarded by placental damage; 2) if the effects of nutrients on fetal growth are mediated through changes in growth promoting hormones; 3) if effective supplementation can be provided via intraamniotic or umbilical venous routes; 4) if the preferential distribution of nutrients to fetal upper body organs is altered in growth retardation or by nutrient supplementation. Chronically catheterized, pregnant sheep will be prospectively followed over the third trimester. In a series of studies, we will compare: normal animals; animals growth retarded by embolization of the maternal side of the placenta; animals growth retarded by maternal, protein-calorie, dietary restriction; and animals of each type given intra-uterine nutritional supplements. Amino acid, glucose and acetate supplements will be infused, over the last month of gestation, via intraamniotic, umbilical venous or fetal intragastric routes. The rate of infusion will equal 1/2 of normal umbilical uptake but will be administered at rates 2 and 4 times greater in studies of nutrient toxicity. In the animal groups, we will follow: fetal growth (the change in weight, crown-rump length and hindlimb length); maternal weight; metabolite levels in fetal blood, maternal blood and amniotic fluid; fetal levels of growth promoting hormones; nutrient delivery to fetal organs; umbilical and hindlimb uptake of nutrients; and fetal organ size and composition. Metabolites measured will be: glucose, Alpha amino nitrogen, alanine, lactate, free fatty acids, acetate, total protein, urea, ammonia, triglycerides, cholesterol, trace minerals, oxygen and blood gases. Hormones measured will be GH, insulin, PRL, oCS, somato-medin-C/IGF1, T3, T4 and IGF2. Fetal blood flow will be determined with a radiolabeled microsphere technique. Fetal organs will be analyzed for DNA, protein, fats, water and ash.